Mechanism of Action of insulin:

Insulin binds to the a-subunit of tyrosine kinase receptors, → Activation of tyrosine

kinase activity of B – subunit → Phosphorylation of intracellular proteins → Change in
enzyme activity, gene expression and translocation of Glut-4 transporter→ Glucose
uptake by adipose tissue & Skin.

Indications of insulin:
A) Diabetes Mellitus:
1- Type-1 diabetics, all cases of Insulin Dependent Diabetes Mellitus (IDDM)
2- Type2(NIDDM)
a- Temporary in N.I.D.D. during STRESS periods e.g. Infection & Pregnancy.
b- Permanently in N.I.D.D. with
-Failed Diet regulation +Exercise +Oral hypoglycemics.
-Renal impairment.
3- Emergency treatment of Diabetic Ketoacidosis& Non-ketotic Hyperosmolar
Diabetic coma.
B) Other Indications: Hyperkalemia due to renal failure.

Adverse Effects of Insulin:

1- Hypoglycemia (the most common and most important)
2- Hypersensitivity reactions
3- Hypokalemia
4- Subcutaneous Lipodystrophy
5- Secondary infection due to injection.
6- Somogyi Effect > Rebound morning hyperglycemia.
7- Weight gain.
8- Insulin resistance.

Amylin analog : Pramlintide (Symlin) mechanism of action

i. Reduces glucagon secretion
ii. Delays gastric emptying (mediated by vagus)
iii. Decreases appetite.
iv. Reduces postprandial glucose elevation
Amylin analog Uses:
Used SC in patients with Type 1 or Type 2 diabetes who have problems with postprandial
hyperglycemia.

Amylin analog Adverse effects:

Nausea, anorexia, hypoglycemia, headache
Sulfonylurea Mechanism of Action:
1- Increase insulin release from the pancreas:
a- It is the main action of sulfonylureas, so their action depends on the presence
of performed endogenous insulin (about 30% functioning -cells)
b- They Block ATP-sensitive K-channel→ Depolarization → Influx of Ca → Exocytosis
→ ↑Release of Insulin.
2- Other actions (Extra-pancreatic): sulfonylureas may reduce hepatic glucose
production and increase peripheral insulin sensitivity.

Indications of Sulfonylureas:
1- Type-2 Diabetes (NIDD) after failure of Diet regulation &exercise.
a- Non-Obese (Sulphonylureas increase appetite).
b- Non-Complicated Diabetes:
- No stress e.g, Operation or Pregnancy.
- No Major organ disease e.g. Cardiac, hepatic or renal.
- No History of diabetic ketoacidosis.
2- Chlorpropamide → Treat Diabetes insipidus.

Adverse Effects of Sulfonylureas:

1- Common adverse effects:
a- Hypoglycemia
b- Weight gain
c- Failure (Primary - Secondary)
2- Teratogenicity and hypoglycemia of fetus.
3- Hypersensitivity

Mechanism of action of biguanides:

1- The primary effect is to reduce hepatic glucose production by activating the enzyme
AMP-dependent protein kinase (AMPK). This leads to stimulation of hepatic fatty acid
oxidation, glucose uptake, and nonoxidative glucose metabolism and reduction of
lipogenesis and gluconeogenesis &glycogenolysis.
2- Other effects
a- Increases insulin sensitivity in muscle, improving peripheral glucose uptake
and utilization.
b- Delays intestinal glucose absorption.

Therapeutic Uses of Metformin:

Used alone or in comb. with other anti-diabetics
● Type 2 (NIDD), in overweight patients, when dietary management and exercise alone
do not result in adequate glycemic control.
● A reduction of diabetic complications after failure of diet

Adverse Effects of Biguanides:

1- GIT: Anorexia, nausea, vomiting, abdominal discomfort, and diarrhea:
2- ↓ absorption of Vitamin B-12.
3- Rarely fatal Lactic Acidosis may occur so
Mechanism of action of GLP-1 analogues
1- Synthetic analogs of Glucagon-like Peptide-1 (GLP-1, an incretin released from GIT
after a meal) → Bind to GLP-1 receptors → reduce postprandial glucose elevation and
glucagon levels, delay gastric emptying, ↑ insulin release &and suppress appetite

Uses GLP-1 analogue

1- control glycemia in patients with type 2 diabetes who fail to achieve control via
metformin and/or sulfonylureas.
2- Liraglutide for weight loss.

Disadvantages GLP-1 analogues :

1. Risk of hypoglycemia when used + sulfonylurea
2. Nausea, anorexia, vomiting
3. Pancreatitis
4. renal impairment and acute renal injury may occur
5. Has to be injected

DPP-4 mechanism of action

Di-Peptidyl Peptidase 4 (DPP-4) enzyme (DPP-4 is an enzyme that breaks down
incretin hormones e.g. GLP-1) leading to prolongation of the action of endogenously
released GLP-1 and GIP

Adverse Effects of DDP-4:

1- Infrequent pancreatitis
2- Saxagliptin → increase risk of heart failure

(SGLT2) INHIBITORS Mechanism of action

▪ inhibiting this transporter will result in glucose excretion of only 30- 50% of the
amount filtered causing glycosuria and lowers glucose levels in patients with type
2 diabetes.
▪ Inhibition of SGLT2 also decreases reabsorption of sodium and causes osmotic
diuresis.
▪ SGLT2 inhibitors may reduce systolic blood pressure

Clinical indication of SGLT-2 inhibitors

● Used as 3rd line therapy for type 2 DM
● Recently, gliflozins are used in the treatment of heart failure as it improves cardiac
contractility

SGLT-2 inhibitors Adverse effects:

1. Genital & urinary tract infections
2. Hypotension
3. Decrease mineral bone density→ risk of fractures
4. Low incidence of hypoglycemia
Mechanism of action of thyroid hormones:
1. T3 and T4 dissociate from Thyroxine-binding globulin (TBG) and enter cells by
diffusion or active transport.
2. Inside the cell, T4 deiodinated to T3
3. T3 enters the nucleus and attaches to its nuclear receptor
4. Drug-receptor complex bind to DNA and promotes transcription of specific gens
mRNA formation → synthesis (production of various enzymes).
Therapeutic Uses of Thyroid Hormones:
1. Replacement therapy in hypothyroidism (levothyroxine)
2. TSH suppression therapy in thyroid cancer and nontoxic goiter.

Mechanism of Action Thioamides :

Thioamides inhibit thyroid hormone synthesis by:-
1. Inhibition of oxidation of iodide to iodine.
2. Inhibition of iodination of tyrosine (organification of iodine).
3. Inhibition of coupling of iodotyrosines to T4 and T3.
4. Propylthiouracil in addition reduces conversion of T4 to T3 in the periphery.
Therapeutic uses Thioamides:
Used in Treatment of hyperthyroidism:
1. As principal therapy.
2. As adjuvant to I 131 to control the disease while waiting its effect.
3. To control the disorder in preparation for surgical treatment.
4. Thyroid storm (PTU inhibits the conversion of T4 to T3)
Adverse effects of Thioamides:
1. Allergy, Agranulocytosis
2. Hepatotoxicity
3. Immunological reactions: e.g. lymphadenopathy,
4. Loss of hair
5. abnormal skin pigmentation

Iodides Mechanism of action :

1. Inhibition of iodide organification
2. Reduction of the response of thyroid gland to TSH,
3. Inhibition of proteolysis of thyroglobulin - &Release of T3& T4.
Iodides Therapeutic indications :
1- Preparation of the patient for thyroidectomy
2. Thyroid crisis (storm) (inhibit hormone release).
3. Prophylactic where goiter is endemic. (Added to salt, water and bread).
Iodides Adverse effects : reversible
1. iodism: (dose-dependent, chronic adverse effects)
a. metallic taste, painful salivary glands, excess salivation, running eyes &nose.
2. Allergic reactions: angioedema, rash, drug fever
Radioactive iodine Mechanism of Action:
1. Oral radioactive iodine is rapidly absorbed &concentrated by thyroid gland
2. It emits Beta rays (cytotoxic) which destroy the gland tissue.
Radioactive iodine Therapeutic uses:
1. Hyperthyroidism in adults over 45 years
2. Hyperthyroidism in patients not fit for surgery
3. Recurrence after medical or surgical treatment, Thyroid cancer.
Radioactive iodine Adverse effects:
1. Hypothyroidism (The chief toxic effect).
2. Thyroid storm (release of thyroid hormone)
3. Patient may require repeated doses.

Therapeutic uses of estrogens

1. Contraception with progestogens.
2. Postmenopausal hormonal therapy(HT):
a. For menopausal symptoms" hot flushes &vaginal atrophy
b. if only vaginal atrophy: use vaginal estrogen
3. Replacement therapy: (estrogen & progestogen) in:
a. 1ry hypogonadism (ovarian failure).
b. Premature menopause
c. Surgical menopause
Adverse Effects of estrogens
1) Nausea and Breast tenderness (most common)
2) Thromboembolic events & myocardial infarction.
3) Salt & water retention leading to edema & hypertension
4) Increased blood sugar levels
5) Risk of breast cancer.
6) Risk of endometrial carcinoma: add progesterone to decrease risk

Therapeutic uses of progestins

1. Oral contraception: alone or with estrogen
2. Functional uterine bleeding.
3. Dysmenorrhea, Amenorrhea, Endometriosis.
Adverse Effects of progestins
1. Weak androgenic actions of some of the progestogens derived from testosterone.
2. Edema
3. Psychic depression.
4. Increase Cholesterol: atherosclerosis

Uses of androgens
Replacement therapy in male 1ry hypogonadism due to deficiency of androgens or 2ry
hypogonadism due to failure of pituitary.
Adverse effects of androgens:
1) Cholestatic jaundice (with testosterone), undesirable sexual activity,
2) masculinization in females, hirsutism, salt retention,
3) early puberty and premature closure of epiphyseal plates in children.
Mechanism of action of cortisol
1- Genomic Mechanism:
- Cortisol is a Steroid i.e. Lipid soluble Gains intracellular access by passive diffusion

Binds to cytoplasmic glucocorticoids receptor (GR-a& GR-B) Activation Receptor-

Hormone complex translocate into the nucleus.
- Receptor-Hormone complex attaches to glucocorticoid response elements and act
- as a transcription factor to express or repress genes depending on the tissue.
a) Gene expression DNA transcription mRNA Protein synthesis e.g.
Lipocortin- I(Annexin-1) &catabolic enzymes.
b) Gene repression Inhibition of protein synthesis (Catabolic) Decreases
cyclooxygenase I| (COX-I), Nitric Oxide Synthase (NOS), inflammatory
mediators & immunoglobulins (Antibodies).
2- Non-genomic Mechanism:
e.g. cortisol can stimulate membrane receptors in Hippocampus.

Therapeutic Uses of Glucocorticoids :

A) Replacement therapy in adrenocortical insufficiency (Addison'sdisease) :
a) Acute Addisonian Crisis:
b) Chronic Addison's Disease:
B) Supplementary & Suppressive therapy
1. Anti-Inflammatory: treat inflammation in:
a. Encephalitis, cerebral edema.
b. Nephritis & nephritic syndrome.
2. Allergic diseases: in the skin, eye & bronchial asthma.
3. Immunosuppressive in:
a. Auto-immunediseases:
b. Suppress tissue & organ rejection.
4. Shock & Stress conditions.
5. Hypervitaminosis D & Hypercalcemia.

Adverse Effects of Glucocorticoids:

A- Short-term treatment:
- insomnia
- behavioral changes (as hypomania)
- acute peptic ulcers
B- Long-term treatment:
1. Metabolic adverse effects
a. Fats: Moon face & Buffalo hump
b. Osteoporosis
c. Na retention: Edema and Hypertension
2. Cataract & increases intra-ocular pressure ›-Glaucoma.
3. Thromboembolic manifestations.
4. Psychological disturbances.
5. Teratogenicity & Retardation of growth in children..
Contraindications of Glucocorticoids:.
1- Diabetes mellitus.
2- Osteoporosis.
3- Hypertension.
4- Peptic ulcer.
5- Psychological disturbances.
6- During pregnancy.
7- Glaucoma.

Calcitonin Action:
• Hypocalcemic hormone (Effects are opposite to those of P.T.H.)
• Decreases Ca++ level in the blood (when Ca++ level increased above normal).
1) Bone: inhibits osteoclastic activity so, it decreases bone resorption.
2) Kidney: inhibits calcium and phosphate reabsorption by the kidney tubules.

Used in
- hypercalcemia &osteoporosis and Paget's disease.
- relief of pain associated with osteoporotic fracture.
- may be beneficial in patients who have recently suffered a vertebral fracture.

Action of biphosphonates
- Bisphosphonates decrease osteoclastic bone resorption via:
1. Decrease in osteoclastic formation/activation.
2. Increase in osteoclastic apoptosis (programmed cell death), and
3. Inhibition of the cholesterol biosynthetic pathway important for osteoclast
function.

Adverse effects of biphosphonates:

- Esophagitis and esophageal ulcers.
- Contraindicated in renal impairment, peptic ulcer.

Teriparatide
- Teriparatide is a recombinant segment of human parathyroid hormone that is
administered subcutaneously SC for the treatment of osteoporosis.
- It is given subcutaneously once daily

- Bone formation is the predominant effect by preferentially stimulating osteoblastic

activity over osteoclastic activity.

- Teriparatide should be reserved for patients at high risk of fractures.

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AntiEpileptic Antidepressant of dopaminergic nigrostriatal nerve terminals occurs
later)
inhibitor as carbidopa to 1 central L-Dopa.
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MOA trials
◦Block Na+-channel
◦Antagonize excitatory transmitters
e.g. Glutamate &Aspartate.
Adverse effects →Sedation &confusion.
c B. Fungistatic in Tinea of Skin (Salicylic acid +Benzoic acid).
C. Antiseptic in Hyperhidrosis (Salicylic acid + Talcum powder).
2. Methyl-Salicylate (Oil of Wintergreen) →Counter-irritant in Arthritis &Myositis.
B) Systemic Uses:
1. Anti-pyretic→ Non-specific &Non-causal.
Adverse Effects of Morphine 2. Analgesic in Mild superficial pains e.g. Headache, toothache, myalgia .
1. Interfere with proper diagnosis of Head injury 3. Effective in dysmenorrhea (PG) but may Increase Bleeding.
&Acute abdomen. 4. Common cold →Treat Fever, headache, muscle and joint pains.
2. Inhibition of Respiration 5. Rheumatic fever (Arthritis)
3. Pin point pupil (PPP) 6. Rheumatoid arthritis
4. Nausea &Vomiting 7. Chronic gout (Alkalinize urine &increase Fluid intake).
5. Bronchospasm 8. Antiplatelet →Prophylaxis against thromboembolic diseases.
6. Constipation
7. Retention of urine
8. Neonatal asphyxia
9. Itching
10. Tolerance &cross-tolerance with other Opioids. AEs
1. Salicylism: Large dose for Long time →Tinnitus, bluring of vision, GIT
upset, irritability &hyperventilation. Reversible
2. Hypoprothrombinemia →Bleeding tendency.
SHGARTINA.HN 3. G.I.T. irritation →Nausea, vomiting, pain, ulceration &bleeding
4. Allergy (Hypersensitivity) →Rash, urticaria, angioedema &Bronchial
asthma.
5. Reye's syndrome: → Encephalopathy & Hepatotoxicity.
6. Teratogenicity →Cardiac septal defect.
1111 7. Idiosyncrasy →Hemolysis in patients with Favism.
8. Nephropathy.
MOA of Paracetamol
1. Inhibit COX-3 in C.N.S. Mainly Anti-pyretic Analgesic →As potent as Aspirin.
2. Almost No Peripheral Action → Almost No Anti-inflammatory & Almost No effect
on respiration, C.V.S., Platelet aggregation, Gastric acidity, or Uric acid.

Therapeutic uses of Paracetamol

● Antipyretic - Analgesic
● especially in patients who cannot tolerate aspirin e.g.
1. Allergy to Aspirin,
2. Bronchial asthma, Children with viral infection,
3. Bleeding tendency, Peptic ulcer, and gout.

Adverse Effects of Paracetamol

1. Toxicity
a. Toxic dose of Paracetamol →Depletion of Glutathione-SH Hepatotoxic &
Nephrotoxic →Fatal.
b. Management:
I.V. N-Acetylcysteine (Rich in S-H) +Oral Methionine.
2. Allergy (Hypersensitivity)

MOA of Colchicine
A) Anti-Gout Effect:
It binds to Microtubular protein (Tubulin) of polymorph nuclear leucocytes
(P.M.N.L) → Decrease Migration of P.M.N.L. to joints →
NO Phagocytosis of Mono-sodium urate crystals →
NO Ruptures of leukocytes →NO release of lactic acid →
NO Inflammatory acidity
B) Anti-Mitotic Effect Inhibits cell division.
At higher doses, colchicine inhibits mitosis, the risk of serious bone marrow
depression.

Therapeutic Uses of Colchicine

Acute attacks of gout
1. Useful when NSAIDs & corticosteroids are contraindicated or not tolerated.
2. Prophylaxis of Gout
3. Prophylaxis of Familial Mediterranean Fever (Polyserositis).

Adverse Effects of Colchicine

1. G.I.T. →Nausea, vomiting &Diarrhoea.
2. Hepatotoxicity
3. Nephrotoxicity → Haematuria & Oliguria.
4. Bone marrow depression
5. Myopathy.
MOA of Allopurinol
1. Allopurinol is metabolized by Xanthine Oxidase enzyme (XOE) → Aloxanthine.
2. Both Alopurinol & Aloxanthine →Occupy & inhibits X.E. →deceases Synthesis of uric acid.
3. It has NO effect on renal excretion of uric acid.

Therapeutic Uses of Allopurinol

First-line therapy for treatment of Hyperuricemia & chronic Gout between attacks
especially in:
1. Gouty nephropathy &urate renal stones.
2. Associated with the use of Anti-Cancer drugs.
3. If uricosuric drugs are ineffective or contraindicated.

Adverse Effects of Allopurinol

1. Precipitates acute attacks of gout during initiation of treatment
2. C.N.S. →Headache &psychological changes.
3. Allergic skin reaction (mainly rash)
4. G.I.T. disturbances.
5. Hepatomegaly.

Adverse effects and toxicity of LA:

A- Systemic toxicity: is most likely to occur with administration of the amide class.
1. CNS
a. restlessness, tremors.
b. This is followed by respiratory depression, coma, and death from
respiratory failure.
2. Cardiovascular system
a. Bradycardia.
b. Hypotension
B- Local toxicity
1. Nerve damage →prolonged sensory &motor loss.
2. Tissue damage →necrosis due to VC by adrenaline added to LA.
3. Mucosal irritation.

C- Toxicity of spinal anaesthesia

1. Early:
a. Hypotension
b. Treatment by leg elevation - I.V. fluid - sympathomimetics.
2. Late:
a. Septic meningitis.
b. Headache.
Adverse Effects of Penicllins:
1. Allergy
2. Diarrhea due to superinfection, especially after oral Ampicillin:
a. Antibiotic-associated (Pseudomembranous) colitis.
3. CNS irritation (seizures) may occur with large doses.
4. Ampicillin induces skin rash in some patients.
5. Benzathine penicillin → Pain, at site of injection.
6. Nafcillin case neutropenia
7. Oxacillin can cause hepatitis.

Adverse Effects of Cephalosporins:

1. Allergy & partial Cross-allergy with penicillins (10%).
2. GIT upsets and Superinfections.
3. Irritant:
a. I.M. → Painful, so add lidocaine.
b. I.V. → Thrombophlebitis
4. Nephrotoxicity specially Cephaloridine
5. Hypoprothrombinemia

Adverse Effects of Vancomycin

1. Ototoxic.
2. Nephrotoxic.
3. Rapid VI infusion →Histamine release → Red man syndrome & Shock.

Adverse Effects of Aminoglycosides:

1. Ototoxicity:
a. so are contraindicated during pregnancy.
2. Nephrotoxicity
3. Neuromuscular blockade: It is rare.
4. Allergic manifestations

Adverse Effects of Tetracyclines:

1. G.I.T. irritation: Nausea, vomiting,
2. Teeth & Bone Abnormalities
- avoided during pregnancy, and lactation & in children up to 18 years.
3. Hepatotoxicity during pregnancy
4. Nephrotoxicity especially if they are used after their expiry date.
5. Photosensitivity

Adverse Effects of Co-trimoxazole

1. Megaloblastic anemia
2. Allergy (Hypersensitivity):
a. Fever, Photosensitivity
b. Cross-allergy with other Sulfonamides e.g. Diuretics
3. Blood dyscrasias
a. Hemolysis in patients with G6PD deficiency.
b. Bone marrow inhibition.
4. GIT disturbances —> diarrhea &Superinfection.
5. Nephrotoxicity
6. Hepatotoxicity
Adverse Effects of Macrolides
1. Most common is Epigastric pain. Erythromycin > Others. →Non- Compliance
2. Cholestatic jaundice.
3. Large doses of erythromycin → Reversible Ototoxicity.

Adverse Effects of fluoroquinolone:

1. GIT upsets .
2. Allergy: skin rash
3. Photosensitivity, use sunscreens & sunblocks.
4. CNS: Headache, dizziness & confusion, insomnia.
5. Chondrolytic Avoid in pregnancy, lactation, and in children up to age of 18y.
6. Rupture of tendons (Achilles tendon) especially in elderly taking glucocorticoids.
7. Nephrotoxic & Crystaluria.
8. The 3rd generation cause prolongation of Q-T interval avoided in arrhythmia

Adverse Effects of Rifampicin:

1. Orange-red discoloration of secretions e.g. Tears, saliva, sweat, sputum & urine.
2. Allergy → Flu-like syndrome.
3. G.I.T. upset.
4. CNS → Headache, Confusion & Ataxia.

Adverse Effects of I.N.H.:

1. Idiosyncrasy:
a. Peripheral neuritis. : Prevented by Pyridoxine (Vit B-6)
2. Acetyl -Isoniazid Hepatotoxicity.
3. Hemolysis in Patients with Favism
4. Drug Interactions:
a. Isoniazid → Enzyme Inhibitor → ↓ Metabolism of Phenytoin → Its plasma
level.
b. Rifampicin → Enzyme Inducer →↑ Acetylation of I.N.H. →↑ Hepatotoxicity.

Therapeutic uses of penicillins

- Treatment of infections caused by bacteria other than G-ve bacteria
1- Infections by gram +ve Cocci: Streptococcal & Staphylococcal infections
2- gram -ve Cocci: Meningococcal meningitis, Gonorrhea.
3- Gram +ve Bacilli : Anthrax, Diphtheria, Tetanus & Gas gangrene.
- Treatment of infections caused by gram-negative bacteria
5- Gram-negative Bacilli → Use Ampicillin & Amoxicillin:
6- Pseudomonas: Anti-pseudomonal penicillin combinations
- Prophylactic uses
1- Streptococcal infection in Rheumatic fever:
Benzathine penicillin
2- Bacterial endocarditis:
Procaine penicillin
In patients with rheumatic fever or prosthetic cardiac valves. before dental
procedures
3- Gonorrheal neonatal ophthalmia:
Benzyl penicillin eye drops.
Therapeutic Uses of Cephalosporins:
1. Pseudomonal infections: Cefoperazone, Ceftazidime and cefepime
2. Anaerobic infections (intra-abdominal, Pelvic de Gyn): Cefoxitin, 3rd & 4 gens
3. Typhoid fever: Ceftriaxone or cefoperazone
4. Respiratory tract infections
5. Urinary tract infections
6. Pre-operative surgical prophylaxis.

Therapeutic Uses of Aminoglycosides:

А) Systemic use:
Used in serious gram-negative infections , Staphylococcal & Enterococcal infections.
1. When Pseudomonal infections it may be necessary to add a beta-lactam with
antipseudomonal action such as piperacillin/tazobactam [Tazocin]
2. Bacterial endocarditis. Add Benzyl penicillin.
B) Topical uses:
1. Topical gentamicin cream, in burns, wounds & skin lesions.
2. Oral neomycin for gut de-contamination
C) Used in TB

Therapeutic Uses of Vancomycin:

1. IV in MRSA & Enterococcal infections.
2. IV prophylactic before dental operations in patients with prosthetic valves.
3. Orally in pseudomembranous colitis.

Therapeutic Uses of Tetracyclines: MACC

1. Mixed bacterial infections of, the respiratory tract (bronchitis, sinusitis).
2. Amoebic dysentery
3. Acne
4. Cholera: ttt & prophylaxis
5. Venereal disease

Therapeutic Uses of Macrolides: ABCDs

-Drug of CHOICE in
1. Atypical Pneumonia caused by Mycoplasma & Legionella.
2. Bordetella pertussis.
3. Chlamydial infection: Respiratory, Genital & ocular.
4. Diphtheria.
5. Sexually transmitted diseases (STD): (Gonorrhea, Syphilis & Chlamydia)

Therapeutic uses of fluoroquinolones: uro git 2 resp

1. Infections of urogenital & GIT tract caused by gram-negative organisms.
2. Respiratory, skin & soft tissue infection.
3. Gonorrhea & Resistant T.B
4. Typical & atypical pneumonia

Therapeutic Uses of co – trimoxazole :

1. Urinary tract infection (UTI).
2. Prostatitis.
3. Gonococcal infection (Urethral & Oropharyngeal).
4. Shigella & Salmonella enteritis
5. Nocardiosis.( Drug of CHOICE).
Therapeutic Uses of Rifampicin:
1. First line drug in T.B. + Isoniazid.
2. Leprosy.
3. Drug of choice in prophylaxis of Meningococcal meningitis
4. Resistant bacterial infections e.g. Staph.

Mechanism of Action of B-lactams: bactericidal

1. They bind to specific Penicillin-Binding-Protein (PBP):
a. Inhibit Transpeptidase enzyme responsible for cross-linking of peptidoglycans, a
final step in cell wall synthesis → Cell Wall Synthesis.
b. Activate Autolysins → Lysis of cell wall.
c. Bacteria imbibe water and DEATH of the microbe.

Mechanism of Action of Vancomycin

Inhibits early steps of Cell wall synthesis →Peptidoglycan polymerization →Bactericidal.

Mechanism of Action of Aminoglycoside :

1. They bind to 30 S ribosomal subunit leading to inhibition of bacterial protien synthesis

2. Aminoglycosides concentrate inside bacteria by O2-requiring active transport

mechanism so they are NOT effective against Anaerobes.

Mechanism of Action of Tetracyclines:

Anti-Bacterial Activity of Tetracyclines:
● Concentrated in bacteria by specific transport proteins unique to the bacterial
cytoplasmic membrane. Attach to 30S ribosomal subunits leading to inhibition of
protein synthesis.
● Bacteriostatic Antibiotics.

Mechanism of Action of Quinolones & Fluoroquinolones

● BACTERICIDAL
● They enter the bacteria by passive diffusion through the porins → inhibit Bacterial
Topoisomerase II (DNA gyrase) & Topoisomerase VI enzymes → prevents the relaxation of
supercoiled DNA required for normal transcription and replication

Mechanism of Action of Rifampicin:

1. Bactericidal.
2. DNA-dependent RNA polymerase enzyme inhibitor

Mechanism of Action of I.N.H.:

1. Tuberculo - Static & Cidal.
2. Decrease Mycolic acid synthesis, Decrease synthesis of Cell Wall.

Mechanism of Action of amphotericin

Amphotericin B binds to ergosterol in the fungal cell membrane → forming amphotericin
B-associated pores in the cell membrane → ↑ permeability of the fungal cell → leakage of
fungal cell contents.
Fungicidal.
N.B.: The human cell membrane contains cholesterol not ergosterol, however; amphotericin B
can bind to human cell membrane, and this could be the cause of its prominent toxicity.
Therapeutic uses of amphotericin
1- Fungal meningitis: given intrathecal, but may cause seizures
2- Fungal pneumonia.
3- Systemic candidiasis (candedemia).
Adverse effects of amphotericin
A- Immediate reaction (infusion-related):
● Manifestations: fever, chills, muscle spasms, headache, hypotension

B- Cumulative toxicity:
1. Hypokalemia, hypomagnesemia, and acidosis.
2. Nephrotoxicity: prevented by increasing renal perfusion by IV saline infusion
before and after amphotericin B infusion.
3. Hepatotoxicity.
4. Anemia (bone marrow inhibition).
5. Seizures after intrathecal administration.

KETOCONAZOLE
● It has a greater ability to inhibit mammalian cytochrome P450 enzymes as it is
less selective for fungal P450 than the newer azoles.
● Used only topically as shampoo in the treatment of
○ seborrheic dermatitis
○ pityriasis versicolor.

ITRACONAZOLE
● it is used exclusively in the treatment of
○ dermatophytes and anychomycosis.

FLUCONAZOLE
● Has the least effect of all the azoles on hepatic microsomal enzymes.
● Has the widest therapeutic index of the azoles.
● The azole of choice in the
○ treatment and prophylaxis of cryptococcal meningitis.
○ IV treatment of candidemia like amphotericin B
○ Has no activity against aspergillosis.

VORICONAZOLE
● An inhibitor of mammalian CYP3A4 and dose reduction of a number of
medications is required when voriconazole is started e.g. HMG-CoA reductase
inhibitors.
● it is the treatment of choice for
○ invasive aspergillosis, and candida.
● Side effects include:
○ rash
○ elevated hepatic enzymes.
○ Visual disturbances are common.
○ Photosensitivity dermatitis in patients receiving chronic oral therapy.

POSACONAZOLE
● Has interactions with substrates of CYP3A4.
● Posaconazole is the broadest spectrum.
○ most species of candida and aspergillus.
○ It is the only azole against agents of mucormycosis.

ISAVUCONAZOLE : Co-administration with strong 3A4 inhibitors is not recommended.